A moisturizing and rejuvenating cream and its application in the prevention and treatment of hand-foot syndrome caused by donafenib tosylate

Abstract

The present invention relates to the technical field of traditional Chinese medicine, and discloses a moisturizing and rejuvenating cream and an application thereof in the prevention and treatment of hand-foot syndrome caused by donafenib tosylate. The moisturizing and rejuvenating cream comprises the following components in parts by mass: 40g of Xinjiang lithospermum erythrorhizon, 40g of angelica sinensis, 40g of gallnut, 20g of sanguisorba officinalis, 20g of Kochia scoparia, 15g of angelica dahurica, 15g of bletilla striata, 20g of phellodendron amurense, 20g of scutellaria baicalensis, 15g of mint, 15g of honeysuckle, 20g of myrrh vinegar, 20g of smilax glabra, 20g of Cnidium monnieri, 30g of Semen Ziziphi Spinosae, and 24g of matrix have the effects of clearing away heat and detoxifying, moistening dryness and promoting tissue regeneration, astringing and relieving itching, and promoting blood circulation and relieving pain. It clears heat without damaging yin, moistens dryness and eliminates pathogenic factors, and has the effect of treating both the symptoms and the root causes. It can effectively prevent and treat HFS related to donafenib tosylate, and has a good effect in improving the quality of life of patients and improving treatment compliance to ensure the smooth implementation of targeted treatment. It is also affordable and easy to use, has good clinical application prospects, and has promotion significance.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and in particular to a clearing and moisturizing cream and an application thereof in the prevention and treatment of hand-foot syndrome caused by donafenib tosylate. Background Art

[0002] With the continuous accumulation of clinical treatment practice and the deepening of medical experiments, treatment plans for malignant tumors are becoming increasingly personalized and precise. Most cancer types can be treated with molecularly targeted drugs based on mutation targets detected by genetic testing. Compared to previous anti-cancer therapies, these drugs are more targeted and more effective, making them a hot research topic in oncology. Furthermore, their increasing affordability makes them accessible to most cancer patients. However, the incidence of skin adverse reactions associated with molecularly targeted drugs is high, particularly hand-foot syndrome. Primary liver cancer (PHC) is the sixth most common cancer worldwide, characterized by high malignancy and rapid progression. Hepatocellular carcinoma (HCC) is a highly prevalent cancer in my country, with a poor prognosis for patients in the middle and late stages. Among the various drugs available for the treatment of HCC, donafenib tosylate is more effective and offers greater hope for prolonging patient survival. However, the incidence of hand-foot syndrome (HFS) associated with donafenib tosylate reaches 52%, impacting patients' quality of life and ensuring that donafenib is used on time and in the correct dosage, which will inevitably affect treatment efficacy and patient survival.

[0003] Hand-foot syndrome (HFS) falls under the category of "dryness and numbness" in Traditional Chinese Medicine (TCM). Its clinical manifestations include swelling or erythema, dryness, scaling, chapped skin, itching, pain, and even pustules on the hands and feet. Dryness is a yang pathogen that can damage body fluids and consume blood, causing erythema, dryness, scaling, and chapped skin. This leads to a depletion of Ying Yin (Yin) and insufficient replenishment of Ying and blood in the limb meridians, resulting in poor blood circulation. This can lead to localized blood stasis, resulting in malnutrition of the hands and feet, causing itching, swelling, and pain. Dryness, toxins, and blood stasis accumulate in the hands and feet, corrupting the skin and causing pustules and even bleeding, forming a pathogenesis of "dryness and heat damaging Yin." While these symptoms are not life-threatening, they can severely impact patients' quality of life. They can reduce their compliance with treatment, necessitating dose reductions in targeted medications, or even leading to discontinuation of treatment, compromising anti-tumor efficacy. Therefore, identifying effective, low-side-effect, and affordable methods for preventing and treating HFS is of great clinical value.

[0004] Currently, there is no unified treatment plan for hand-foot syndrome. Western medicine uses high-dose vitamin B6, the COX-2 inhibitor celecoxib, glucocorticoids, and urea creams, but these treatments are ineffective and can be very irritating to patients. Traditional Chinese medicine (TCM) offers advantages in preventing and treating hand-foot syndrome. Existing TCM preparations for this condition are mostly oral, which can increase the gastrointestinal burden on cancer patients and potentially affect the function of other organs. External TCM treatments have a good clinical efficacy for hand-foot syndrome associated with molecularly targeted anti-tumor therapy, are easy to use, and have good compliance. Externally applied ointments are more convenient and more effective than fumigation and washing decoctions.

[0005] Therefore, the present invention provides a new Chinese medicine composition made of Qingrun Huanfu cream, which is used for hand-foot syndrome after treatment with donafenib tosylate, and has great significance. Summary of the Invention

[0006] In order to solve the above technical problems, the present invention provides a moisturizing and rejuvenating cream and its application in the prevention and treatment of hand-foot syndrome caused by donafenib tosylate, providing a moisturizing and rejuvenating cream with low cost, good efficacy, easy use and no toxic side effects.

[0007] In order to achieve the above object, the present invention discloses a moisturizing and rejuvenating skin cream, comprising the following components in parts by weight: 35-46 parts of Xinjiang lithospermum erythrorhizon, 32-48 parts of angelica sinensis, 32-45 parts of gallnut, 16-28 parts of sanguisorba officinalis, 15-24 parts of kochia scoparia, 12-17 parts of angelica dahurica, 10-18 parts of bletilla striata, 16-22 parts of phellodendron amurense, 18-23 parts of scutellaria baicalensis, 11-18 parts of mint, 10-20 parts of honeysuckle, 17-25 parts of vinegar myrrh, 18-26 parts of smilax glabra, 16-24 parts of cnidium monnieri, 26-34 parts of south jujube seed, and 18-30 parts of base;

[0008] The preparation method of the moisturizing and rejuvenating cream comprises the following steps:

[0009] Weigh each raw material by mass, crush it into fine powder, sieve it, soak it in distilled water for 30-40 minutes, heat it, boil it for 30-60 minutes, concentrate it to obtain a concentrate, add the base, boil it over low heat until it becomes a paste, and obtain the moisturizing and rejuvenating cream.

[0010] Preferably, the mass ratio of the fine powder to distilled water is 1:5-10.

[0011] Preferably, the matrix consists of stearic acid and beeswax.

[0012] Preferably, the mass ratio of stearic acid to beeswax is 1:3.

[0013] Preferably, the moisturizing and rejuvenating cream comprises the following components in parts by mass: 38-45 parts of Xinjiang lithospermum, 34-46 parts of angelica, 35-44 parts of gallnut, 17-24 parts of sanguisorba officinalis, 18-22 parts of kochia scoparia, 13-16 parts of angelica dahurica, 12-16 parts of bletilla striata, 17-21 parts of phellodendron, 18-22 parts of scutellaria, 12-17 parts of mint, 12-19 parts of honeysuckle, 18-24 parts of vinegar myrrh, 18-24 parts of smilax glabra, 18-24 parts of cnidium monnieri, 28-34 parts of south jujube seeds, and 20-26 parts of base.

[0014] Preferably, the moisturizing and rejuvenating cream comprises the following components in parts by mass: 39-42 parts of Xinjiang lithospermum, 35-45 parts of angelica, 38-42 parts of gallnut, 19-21 parts of sanguisorba officinalis, 18-20 parts of kochia scoparia, 14-15 parts of angelica dahurica, 14-16 parts of bletilla striata, 18-20 parts of phellodendron, 18-21 parts of scutellaria, 13-16 parts of mint, 14-16 parts of honeysuckle, 19-22 parts of vinegar myrrh, 18-21 parts of smilax glabra, 18-22 parts of cnidium monnieri, 28-32 parts of south jujube seeds, and 20-25 parts of base.

[0015] Preferably, the clearing and rejuvenating cream comprises the following components in parts by mass: 40g of Xinjiang lithospermum, 40g of angelica sinensis, 40g of gallnut, 20g of sanguisorba officinalis, 20g of kochia scoparia, 15g of angelica dahurica, 15g of bletilla striata, 20g of phellodendron amurense, 20g of scutellaria baicalensis, 15g of mint, 15g of honeysuckle, 20g of vinegar myrrh, 20g of smilax glabra, 20g of cnidium monnieri, 30g of south jujube seed, and 24g of base.

[0016] Preferably, the Qingrun Huanfu Cream is used in the prevention and treatment of hand-foot syndrome caused by donafenib tosylate.

[0017] Compared with the prior art, the present invention has the following chemical mechanisms and beneficial technical effects:

[0018] (1) The Qingrun Huanfu Cream prepared in the present invention is based on the pathogenesis of hand-foot syndrome. After repeated clinical preparation and practice, it is formulated into Qingrun Huanfu Cream. Clinical observation shows that it is effective in preventing and treating hand-foot syndrome caused by the oral molecular targeted drug donafenib tosylate. The Xinjiang Lithospermum in the formula clears heat and cools blood, promotes blood circulation and removes toxins, the Angelica sinensis nourishes yin and moistens dryness, promotes blood circulation and relieves pain, and the South Ziziphus jujuba seed detoxifies, astringes and promotes tissue regeneration, which are all the main drugs; Phellodendron chinense, Scutellaria baicalensis, and Smilax glabra clear heat and detoxify, while Bletilla striata, Gallnut chinensis, and South Ziziphus jujuba seed astringe and promote tissue regeneration, reduce swelling and stop bleeding, which are all the ministerial drugs to enhance the monarch drugs' heat-clearing, blood-activating, astringent and tissue regeneration effects; Sanguisorba officinalis cools blood and detoxifies, astringes sores and stops bleeding, Cnidium monnieri and Kochia scoparia clears heat and relieves itching, Angelica dahurica relieves swelling and relieves itching, and Myrrha vinegar disperses blood stasis and relieves pain, reduces swelling and promotes tissue regeneration, which are all the adjuvant drugs, one is to enhance the detoxification and astringent effect, and the other is to clear heat and relieve itching; Honeysuckle and mint both enter the lung meridian, and the lung and skin are the exterior and interior, which can clear away evil and expel pathogens, so they are the guiding drugs; looking at the whole prescription, it has the effects of clearing heat and detoxifying, moistening dryness and promoting tissue regeneration, astringing and relieving itching, promoting blood circulation and stopping pain, clears heat without damaging yin, moisturizes dryness and removes evil, and has the effect of treating both the symptoms and the root causes.

[0019] (2) The present study showed that the incidence of HFS in the treatment group was lower than that in the control group after one month of treatment with donafenib tosylate, indicating that Qingrun Huanfu Cream can indeed effectively prevent the occurrence of HFS associated with donafenib tosylate; the incidence of grade 2 and 3 HFS in the treatment group was low, indicating that Qingrun Huanfu Cream can relieve the symptoms of HFS associated with donafenib tosylate and has a good attenuating effect; the number of cases in the treatment group where the dose of donafenib tosylate was reduced due to HFS was less than that in the control group, and there was no case of drug discontinuation, indicating that Qingrun Huanfu Cream can improve the patient's compliance with targeted drug treatment and ensure the continuous treatment of targeted drugs to a large extent, thereby ensuring the efficacy of targeted drugs; the DLQI score of the treatment group after taking donafenib tosylate for one month was lower than that of the control group, confirming that Qingrun Huanfu Cream can improve the quality of life of patients receiving targeted drug treatment and has a positive effect on increasing patient compliance with treatment. It can be seen from the experimental data that the Qingrun Huanfu Cream prepared in the present invention can effectively prevent and treat HFS associated with donafenib tosylate, and has a good effect on improving the quality of life of patients and improving treatment compliance to ensure the smooth implementation of targeted treatment. It is also affordable and easy to use, has good clinical application prospects, and has promotion significance. DETAILED DESCRIPTION

[0020] The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0021] Example 1

[0022] A moisturizing and rejuvenating skin cream comprises the following components in parts by mass: 40g of Xinjiang lithospermum, 40g of angelica sinensis, 40g of gallnut, 20g of sanguisorba officinalis, 20g of Kochia scoparia, 15g of angelica dahurica, 15g of bletilla striata, 20g of phellodendron amurense, 20g of scutellaria baicalensis, 15g of mint, 15g of honeysuckle, 20g of vinegar myrrh, 20g of smilax glabra, 20g of cnidium monnieri, 30g of spinach seed, and 24g of a base.

[0023] The relevant performance tests were performed on the Qingrun Huanfu Cream prepared in the embodiment of the present invention:

[0024] Sixty-four patients with advanced hepatocellular carcinoma who received oral donafenib tosylate tablets as first-line treatment at Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine between July 2021 and July 2022 were randomly divided into a treatment group and a control group, with 32 patients in each group. The treatment group included 19 males and 13 females aged (68.0±11.0) years, with a KPS score of 68.8±3.7. Twenty-one patients had Child A liver function class, 11 had Child B liver function class, and none had Child C liver function class. Disease stage: 3 patients at stage II, 10 at stage III, and 19 at stage IV. The control group included 21 males and 11 females aged (68.0±11.0) years, with a KPS score of 69.2±3.4. Twenty-three patients had Child A liver function class, 9 had Child B liver function class, and none had Child C liver function class. Disease stage: 2 patients at stage II, 11 at stage III, and 19 at stage IV. There was no statistically significant difference in clinical data such as gender, age, physical strength score, liver function, and disease stage between the two groups of patients (P>0.05), and the two groups were comparable.

[0025] Diagnostic criteria: The HFS grading criteria for acute and subacute toxic reactions of antineoplastic drugs developed by the National Cancer Institute (NCI) of the United States were used as a reference;

[0026] Inclusion criteria: Patients diagnosed with PHC by pathology or clinical examination and who had not received Western medical anti-tumor intervention; Karnofsky score > 60 points; no obvious abnormalities in heart, liver, or kidney function; expected survival time > 2 months; aged 18-70 years; informed consent;

[0027] Exclusion criteria: patients with underlying skin diseases; patients with significant abnormalities in heart, liver, and kidney function; patients who have received chemotherapy or targeted therapy; pregnant women or patients with mental illness; patients with poor compliance;

[0028] Dropout criteria: those with poor compliance who did not follow the skin care measures on time; those who discontinued treatment due to obvious toxic side effects; those who received other Western medicine anti-tumor treatments during the period; those who withdrew on their own or were lost to follow-up; those with incomplete data.

[0029] Treatment: Both groups received general hand and foot skin care (maintaining cleanliness and hygiene, washing regularly, and administering antibiotics if infection occurs). The control group soaked their hands and feet in warm water, dried them, and evenly applied a lotion or lubricant containing urea and corticosteroids to the affected area twice daily, starting with oral administration of donafenib tosylate. The treatment group soaked their hands and feet in warm water, dried them, and evenly applied a moisturizing and refreshing cream to the affected area twice daily, starting with oral administration of donafenib tosylate.

[0030] Patients with primary liver cancer who were receiving first-line treatment with donafenib tosylate were randomly divided into a trial group and a control group of 32 patients. The control group received a lotion or lubricant containing urea and corticosteroids applied to their hands and feet, while the treatment group received Qingrun Huanfu Cream applied to their hands and feet. After one month of treatment, the incidence of HFS, dose reduction or discontinuation of donafenib tosylate due to HFS, and DLQI scores were compared between the two groups. The clinical efficacy of Qingrun Huanfu Cream in preventing and treating donafenib tosylate-related hand-foot syndrome (HFS) was observed. The results are shown in the table:

[0031] Table 1 Comparison of HFS incidence and targeted drug reduction or discontinuation between the two groups [cases (%)]

[0032]

[0033] ①P<0.05, compared with the control group; ②P>0.05, compared with the control group.

[0034] As shown in Table 1, the incidence of HFS and the incidence of targeted drug reduction or discontinuation were significantly lower in the treatment group (31.2%) and the control group (56.3%) after one month of treatment (P < 0.05). There was no statistically significant difference in the incidence of grade 1 HFS between the two groups (P > 0.05). The incidence of grade 2 and 3 HFS in the treatment group was significantly lower than that in the control group (12.5% ​​vs. 21.9%, 0.0% vs. 9.4%) (P < 0.05). HFS led to dose reduction or discontinuation of donafenib tosylate in 10 patients (31.2%) in the control group and in 4 patients (12.5%) in the treatment group, with no discontinuation. The difference between the two groups was statistically significant (P < 0.05).

[0035] Efficacy assessment

[0036] Hand-foot syndrome assessment: Based on the HFS grading criteria for acute and subacute toxic reactions to antineoplastic drugs developed by the National Cancer Institute (NCI), the incidence of HFS and the number of patients who discontinued or reduced the dose of donafenib tosylate due to HFS were counted.

[0037] Quality of life: The changes in quality of life of the two groups of patients before and after treatment were compared based on the Life Quality Index (DLQI) scale;

[0038] Statistical methods: SPSS 21.0 statistical software was used for statistical analysis and processing of research data. Paired sample t test was used for data, and chi-square test was used for count data, with P < 0.05 indicating statistical significance;

[0039] Comparison of DLQI scores: There was no significant difference in the DLQI scores between the two groups before treatment (P>0.05). After treatment, the DLQI score of the control group was (9.32±2.43) and the DLQI score of the treatment group was (5.26±2.38), which was lower in the treatment group than in the control group (P<0.05). The results are shown in Table 2:

[0040] Table 2 Comparison of DLQI scores between the two groups (points, )

[0041]

[0042] ①P<0.05, compared with the control group; ②P>0.05, compared with the control group.

[0043] The incidence of HFS in the treatment group after taking donafenib tosylate for one month was significantly lower than that in the control group (31.2% & 56.3)% (P < 0.05); there was no statistically significant difference in the incidence of grade 1 HFS between the two groups (P > 0.05), while the incidence of grade 2 and 3 HFS in the treatment group was lower than that in the control group (21.9%, 9.4% & 12.5%, 0.0%), and the difference was statistically significant (P < 0.05); HFS led to a reduction or discontinuation of donafenib tosylate. There were 10 cases (31.2%) in the control group and 4 cases (12.5%) in the treatment group. The difference between the two groups was statistically significant (P < 0.05). After treatment, the DLQI score of the control group was (9.32 ± 2.43), and the DLQI score of the treatment group was (5.26 ± 2.38). The score of the treatment group was lower than that of the control group (P < 0.05). Qingrun Huanfu Cream can prevent and treat hand-foot syndrome caused by donafenib tosylate, and is worthy of clinical promotion.

[0044] Although the embodiments of the present invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and variations may be made to these embodiments without departing from the principles and spirit of the present invention. All equivalent changes and improvements made within the scope of the present invention should still fall within the scope of the patent coverage of the present invention.

Claims

1. A Chinese medicine composition for hand-foot syndrome, characterized in that: It is made from the following components by weight: 40g of Xinjiang Lithospermum officinale, 40g of Chinese Angelica sinensis, 40g of Gallnut, 20g of Sanguisorba officinalis, 20g of Kochia scoparia, 15g of Angelica dahurica, 15g of Bletilla striata, 20g of Phellodendron amurense, 20g of Scutellaria baicalensis, 15g of Menthol, 15g of Honeysuckle Flos, 20g of Myrrh, 20g of Smilax glabra, 20g of Cnidium monnieri, 30g of Semen Ziziphi spinulosae, and 24g of base.

2. A Chinese medicine composition for hand-foot syndrome according to claim 1, characterized in that, The preparation method of the traditional Chinese medicine composition for hand-foot syndrome comprises the following steps: Weigh each raw material by mass, crush it into fine powder, sieve it, soak it in distilled water for 30-40 minutes, heat it, boil it for 30-60 minutes, concentrate it to obtain a concentrate, add the matrix, boil it over low heat until it becomes a paste, and thus obtain a traditional Chinese medicine composition for hand-foot syndrome.

3. A Chinese medicine composition for hand-foot syndrome according to claim 2, characterized in that, The mass ratio of the fine powder to distilled water is 1:5-10.

4. A Chinese medicine composition for hand-foot syndrome according to claim 2, characterized in that, The base consists of stearic acid and beeswax.

5. A Chinese medicine composition for hand-foot syndrome according to claim 4, characterized in that, The mass ratio of the stearic acid to the beeswax is 1:

3.

6. Use of the traditional Chinese medicine composition for hand-foot syndrome according to claim 1 in the preparation of a drug for preventing and treating hand-foot syndrome caused by donafenib tosylate.

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